血清肌肉生长抑制素和肌肉环指蛋白-1对慢性阻塞性肺疾病急性加重期并发肺动脉高压的预测价值

Values of serum myostatin and MuRF-1 to the prediction of pulmonary hypertension in patients with acute exacerbation of chronic obstructive pulmonary disease

目的观察慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)急性加重期并发肺动脉高压(pulmonary hypertension,PH)患者血清肌肉生长抑制素(myostatin,MSTN)和肌肉环指蛋白-1(muscle ring finger protein-1,MuRF-1)水平变化,探讨其对COPD急性加重期患者并发PH的预测价值。方法150例COPD患者根据病程分为急性加重期组72例和稳定期组78例,急性加重期组根据平均肺动脉压分为合并PH组(平均肺动脉压≥20 mm Hg)34例和未合并PH组(平均肺动脉压<20 mm Hg)38例;同期100例体检健康者为对照组。采用ELISA法检测各组血清MSTN、MuRF-1水平;采用多因素logistic回归分析COPD急性加重期患者并发PH的危险因素;绘制ROC曲线,评估血清MSTN、MuRF-1水平对COPD急性加重期患者并发PH的预测价值。结果急性加重期组血清MSTN[(297.79±30.86)ng/L]、MuRF-1[(397.52±26.71)ng/L]水平明显高于稳定期组[(244.19±20.88)、(359.11±24.14)ng/L]和对照组[(190.70±25.26)、(283.06±28.45)ng/L](P<0.05),稳定期组高于对照组(P<0.05)。合并PH组血清MSTN[(315.77±14.29)ng/L]、MuRF-1[(418.46±15.47)ng/L]水平明显高于未合并PH组[(274.47±21.73)、(376.01±16.29)ng/L](P<0.05)。MSTN≥295.87 ng/L(OR=1.053,95%CI:1.007~1.100,P=0.022)、MuRF-1≥395.32 ng/L(OR=1.034,95%CI:1.002~1.068,P=0.038)是COPD急性加重期患者并发PH的独立危险因素。血清MSTN、MuRF-1水平最佳截断值分别为297.03 ng/L、395.48 ng/L时,单独及联合检测预测COPD急性加重期并发PH的AUC分别为0.908(95%CI:0.851~0.948,P<0.001)、0.879(95%CI:0.817~0.925,P<0.001)、0.946(95%CI:0.898~0.976,P<0.001),灵敏度分别为89.48%、70.56%、93.89%,特异度分别为80.56%、86.10%、88.71%。血清MSTN、MuRF-1联合检测预测COPD急性加重期并发PH的AUC明显大于MSTN和MuRF-1单独预测(P<0.05)。结论COPD急性加重期并发PH患者血清MSTN、MuRF-1水平明显升高,MSTN、MuRF-1是COPD急性加重期患者并发PH的独立危险因素,二者联合检测可提高COPD急性加重期患者并发PH的预测价值。

Objective To investigate the values of serum myostatin and muscle ring finger protein-1(MuRF-1)to the prediction of pulmonary hypertension(PH)in patients with acute exacerbations of chronic obstructive pulmonary disease(AECOPD)by observing the expressions of myostatin and MuRF-1.Methods Totally 150 patients with chronic obstructive pulmonary disease(COPD)were divided into AECOPD group(n=72)and stable COPD group(n=78).According to the mean pulmonary artery pressure(mPAP),AECOPD group was redivided into PH group(mPAP≥20 mm Hg,n=34)and no-PH group(mPAP<20 mm Hg,n=38).Another 100 healthy volunteers were as controls(control group).ELISA was used to detect the levels of serum myostatin and MuRF-1.Multivariate logistic regression analysis was used to evaluate the risk factors of PH in patients with AECOPD.ROC was drawn to assess the predictive values of serum myostatin and MuRF-1 levels to PH in AECOPD patients.Results The levels of myostatin and MuRF-1 were higher in AECOPD group((297.79±30.86),(397.52±26.71)ng/L)than those in stable COPD group((244.19±20.88),(359.11±24.14)ng/L)and control group((190.70±25.26),(283.06±28.45)ng/L)(P<0.05),higher in stable COPD group than those in control group(P<0.05),and higher in PH group((315.77±14.29),(418.46±15.47)ng/L)than those in no-PH group((274.47±21.73),(376.01±16.29)ng/L)(P<0.05).Myostatin≥295.87 ng/L and MuRF-1≥395.32 ng/L were the independent risk factors of PH in AECOPD patients(OR=1.053,95%CI:1.007-1.100,P=0.022;OR=1.034,95%CI:1.002-1.068,P=0.038).When the optimal cut-offvalues of myostatin and MuRF-1 were 297.03 and 395.48 ng/L,the AUCs of detections of myostatin,MuRF-1 and myostatin+MuRF-1 for predicting PH were 0.908(95%CI:0.851-0.948,P<0.001),0.879(95%CI:0.817-0.925,P<0.001)and 0.946(95%CI:0.898-0.976,P<0.001),the sensitivities were 89.48%,70.56%and93.89%,and the specificities were 80.56%,86.10%and 88.71%,respectively.The AUCof myostatin+MuRF-1 was significantly larger than that of either myostatin or MuRF-1(P<0.05).Conclusion The serum myostatin and MuRF-1 levels elevate obviously in AECOPD patients with PH,both of which are the independent risk factors of PH.The combined detection of myostatin and MuRF-1 can improve the predictive value to PH in AECOPD patients.